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Viral Entry Inhibitors Targeting Six-Helical Bundle Core Against Highly Pathogenic Enveloped Viruses with Class I Fusion Proteins

Author(s):

Jing Pu, Joey Tianyi Zhou, Ping Liu, Fei Yu, Xiaoyang He, Lu Lu* and Shibo Jiang*  

Abstract:


TypeⅠ enveloped viruses bind to cell receptors through surface glycoproteins to initiate infection or undergo receptor-mediated endocytosis. They also initiate membrane fusion in the acidic environment of endocytic compartments, releasing genetic material into the cell. In the process of membrane fusion, envelope protein exposes fusion peptide, followed by insertion into the cell membrane or endosomal membrane. Further conformational changes ensue in which the type 1 envelope protein forms a typical six-helix bundle structure, shortening the distance between viral and cell membranes so that fusion can occur. Entry inhibitors targeting viral envelope proteins, or host factors, are effective antiviral agents and have been widely studied. Some have been used clinically, such as T20 and Maraviroc for human immunodeficiency virus 1 (HIV-1) or Myrcludex B for hepatitis D virus (HDV). This review focuses on entry inhibitors that target the six-helical bundle core against highly pathogenic enveloped viruses with class I fusion proteins, including retroviruses, coronaviruses, influenza A viruses, paramyxoviruses, and filoviruses.

Keywords:

Entry inhibitor, 6-HB, class I fusion proteins, highly pathogenic, HIV virus, enveloped viruses

Affiliation:

Key Laboratory of Medical Molecular Virology of MOE/MOH/CAMS, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, Institute of High Performance Computing, The Agency for Science, Technology, and Research, Institute of High Performance Computing, The Agency for Science, Technology, and Research, College of Life Sciences, Hebei Agricultural University, Baoding, Beijing Institute of Radiation Medicine, Beijing, Key Laboratory of Medical Molecular Virology of MOE/MOH/CAMS, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, Key Laboratory of Medical Molecular Virology of MOE/MOH/CAMS, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032



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